Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein
The mechanisms underlying the selective targeting of specific brain regions by different neurodegenerative diseases is one of the most intriguing mysteries in medicine. For example, it is known that Alzheimer’s disease primarily affects parts of the brain that play a role in memory, whereas Parkinso...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2014-01-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/7/1/21 |
| _version_ | 1818932383165972480 |
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| author | Walker S. Jackson |
| author_facet | Walker S. Jackson |
| author_sort | Walker S. Jackson |
| collection | DOAJ |
| description | The mechanisms underlying the selective targeting of specific brain regions by different neurodegenerative diseases is one of the most intriguing mysteries in medicine. For example, it is known that Alzheimer’s disease primarily affects parts of the brain that play a role in memory, whereas Parkinson’s disease predominantly affects parts of the brain that are involved in body movement. However, the reasons that other brain regions remain unaffected in these diseases are unknown. A better understanding of the phenomenon of selective vulnerability is required for the development of targeted therapeutic approaches that specifically protect affected neurons, thereby altering the disease course and preventing its progression. Prion diseases are a fascinating group of neurodegenerative diseases because they exhibit a wide phenotypic spectrum caused by different sequence perturbations in a single protein. The possible ways that mutations affecting this protein can cause several distinct neurodegenerative diseases are explored in this Review to highlight the complexity underlying selective vulnerability. The premise of this article is that selective vulnerability is determined by the interaction of specific protein conformers and region-specific microenvironments harboring unique combinations of subcellular components such as metals, chaperones and protein translation machinery. Given the abundance of potential contributory factors in the neurodegenerative process, a better understanding of how these factors interact will provide invaluable insight into disease mechanisms to guide therapeutic discovery. |
| first_indexed | 2024-12-20T04:31:37Z |
| format | Article |
| id | doaj.art-a6ff1c6b782d4624b1f020777871e3c3 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-20T04:31:37Z |
| publishDate | 2014-01-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-a6ff1c6b782d4624b1f020777871e3c32022-12-21T19:53:22ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112014-01-0171212910.1242/dmm.012146012146Selective vulnerability to neurodegenerative disease: the curious case of Prion ProteinWalker S. JacksonThe mechanisms underlying the selective targeting of specific brain regions by different neurodegenerative diseases is one of the most intriguing mysteries in medicine. For example, it is known that Alzheimer’s disease primarily affects parts of the brain that play a role in memory, whereas Parkinson’s disease predominantly affects parts of the brain that are involved in body movement. However, the reasons that other brain regions remain unaffected in these diseases are unknown. A better understanding of the phenomenon of selective vulnerability is required for the development of targeted therapeutic approaches that specifically protect affected neurons, thereby altering the disease course and preventing its progression. Prion diseases are a fascinating group of neurodegenerative diseases because they exhibit a wide phenotypic spectrum caused by different sequence perturbations in a single protein. The possible ways that mutations affecting this protein can cause several distinct neurodegenerative diseases are explored in this Review to highlight the complexity underlying selective vulnerability. The premise of this article is that selective vulnerability is determined by the interaction of specific protein conformers and region-specific microenvironments harboring unique combinations of subcellular components such as metals, chaperones and protein translation machinery. Given the abundance of potential contributory factors in the neurodegenerative process, a better understanding of how these factors interact will provide invaluable insight into disease mechanisms to guide therapeutic discovery.http://dmm.biologists.org/content/7/1/21Huntington’s diseaseNeurodegenerationSpinocerebellar ataxiaKnock-in miceNeuropathologyPrion diseases |
| spellingShingle | Walker S. Jackson Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein Disease Models & Mechanisms Huntington’s disease Neurodegeneration Spinocerebellar ataxia Knock-in mice Neuropathology Prion diseases |
| title | Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein |
| title_full | Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein |
| title_fullStr | Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein |
| title_full_unstemmed | Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein |
| title_short | Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein |
| title_sort | selective vulnerability to neurodegenerative disease the curious case of prion protein |
| topic | Huntington’s disease Neurodegeneration Spinocerebellar ataxia Knock-in mice Neuropathology Prion diseases |
| url | http://dmm.biologists.org/content/7/1/21 |
| work_keys_str_mv | AT walkersjackson selectivevulnerabilitytoneurodegenerativediseasethecuriouscaseofprionprotein |